In a number of species the primordial germ cells (PGCs) originate separate from the somatic gonad. During early embryonic development, the PGCs migrate through somatic tissues to their target, the gonadal primordia. The directed migration of PGCs is an active process, thought to be mediated by both attractive and repulsive signals. 3-hydroxy-3- methylglutaryl coenzymeA reductase (HMGCR), a general metabolic enzyme, is both necessary and sufficient to attract migrating germ cells. How HMGCR mediates the guidance of germ cells along a highly characteristic path is not known. The goal of the proposed work is to characterize the role of HMGCR in directing Drosophila PGC migration using both pharmacological and genetic approaches. Pharmacological reagents, including inhibitors of well characterized pathway branches downstream of HMGCR, provide a directed means of identifying which branch of the highly branched pathway is mediating PGC guidance. To identify genetic loci that act downstream of hmgcr, a genetic screen for mutations that dominantly enhance the mild migratory defects of a weak mutation in hmgcr will also be carried out. These experiments will aid in identifying the molecular nature of a germ cell guidance signal produced by the HMGCR pathway and how germ cells receive this signal.